Gene Therapy Clinical Study in Adult PKU (pheNIX)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03952156 |
Recruitment Status :
Active, not recruiting
First Posted : May 16, 2019
Last Update Posted : March 2, 2023
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Condition or disease | Intervention/treatment | Phase |
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Phenylketonurias PAH Deficiency | Genetic: HMI-102 | Phase 1 Phase 2 |
Part 1 of this study will evaluate the safety and efficacy of HMI-102 gene therapy in adult subjects with PKU due to PAH deficiency. Subjects will receive a single dose of HMI-102 administered intravenously. Up to 3 dose levels of HMI-102 may be investigated in this study. At a given dose level, a minimum of 2 subjects will be enrolled and dosed. Dosing of the first two subjects will be staggered. Following evaluation of data from the first 2 subjects in a cohort, a decision can be made to either escalate to the next dose level or expand the cohort at the selected dose level. Additional doses may be added by HMI to investigate intermediate or higher doses.
In Part 2 dose expansion, evaluation of up to 2 dose levels is planned. Subjects will be randomized to receive HMI-102 or a concurrent delayed treatment control arm. Subjects in the delayed treatment control will be eligible to receive HMI-102 after 28 weeks.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 28 participants |
Allocation: | Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1/2 Open-Label, Randomized, Concurrently-Controlled, Dose Escalation Study to Evaluate the Safety and Efficacy of HMI-102 in Adult PKU Subjects With PAH Deficiency |
Actual Study Start Date : | June 10, 2019 |
Actual Primary Completion Date : | January 10, 2023 |
Estimated Study Completion Date : | June 2023 |

Arm | Intervention/treatment |
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Experimental: Cohort 1
Dose Level 1 of HMI-102 delivered intravenously one time
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Genetic: HMI-102
HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene |
Experimental: Cohort 2
Dose Level 2 of HMI-102 delivered intravenously one time
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Genetic: HMI-102
HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene |
Experimental: Cohort 3
Dose Level 3 of HMI-102 delivered intravenously one time
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Genetic: HMI-102
HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene |
Experimental: Delayed Treatment Control
Delayed Treatment Control Arm
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Genetic: HMI-102
Control subjects will generally have the same assessments as treated subjects. Control subjects will undergo pre-baseline procedures to confirm that they are eligible to receive treatment with HMI-102. Once eligible control subjects are dosed with HMI-102, they will initiate the same post-dose procedures as subjects who received HMI-102. |
Experimental: Expansion Phase First Dose level
Expansion Phase First Dose Level of HMI-102 delivered intravenously one time
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Genetic: HMI-102
HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene |
Experimental: Expansion Phase Second Dose level
Expansion Phase Second Dose Level of HMI-102 delivered intravenously one time
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Genetic: HMI-102
HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene |
- Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Escalation Phase) [ Time Frame: Baseline to Week 52 ]Subjects with at least one TEAE or serious TEAE
- Change from baseline in clinical laboratory values (Dose Escalation Phase) [ Time Frame: Baseline to Week 52 ]Change in serum chemistry values including liver function tests, hematology, and urinalysis
- Change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations (Dose Escalation Phase) [ Time Frame: Baseline to Week 52 ]Subjects change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations
- Incidence of sustained plasma Phe concentration of ≤360 μmol/L at 28 weeks post dose (Dose Escalation Phase) [ Time Frame: Week 28 ]Subjects achieving a sustained plasma Phe concentration ≤360 μmol/L at 28 weeks post dose
- Change from baseline in Plasma Phe Concentration (Dose Escalation Phase) [ Time Frame: Weeks 24-28 ]Change from baseline in plasma Phe concentration during Weeks 24-28
- Change from baseline in mean Plasma Phe Concentration (Dose Expansion Phase) [ Time Frame: Weeks 24-28 ]Change from baseline in mean plasma Phe concentration during Weeks 24-28
- Incidence of plasma Phe concentration thresholds up to Week 28 post administration of HMI-102 (Dose Expansion Phase) [ Time Frame: Baseline to Week 28 ]Subjects achieving plasma Phe concentration thresholds up to Week 28 post administration of HMI-102
- Incidence of plasma Phe concentration thresholds up to Week 52 post administration of HMI-102 (Dose Expansion Phase) [ Time Frame: Baseline to Week 52 ]Subjects achieving plasma Phe concentration thresholds up to Week 52 post administration of HMI-102
- Change from baseline in total protein intake at Week 52 post-administration of HMI-102 (Dose Expansion Phase) [ Time Frame: Week 52 ]Subject Achieving a change from baseline in total protein intake at Week 52 post-administration of HMI-102
- Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Expansion Phase) [ Time Frame: Baseline to Week 52 ]Subjects with at least one TEAE or serious TEAE
- Phenylketonuria Quality of Life Questionnaire (PKU-QOL) [ Time Frame: Baseline to Week 52 ]Change in PKU-QOL

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Ages Eligible for Study: | 18 Years to 55 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- Adults 18-55 years of age at the time of informed consent
- Diagnosis of phenylketonuria (PKU) due to PAH deficiency
- Two plasma Phe values with a concentration of ≥ 600 μmol/L drawn at least 72 hours apart during the screening period and at least one historical value ≥ 600 μmol/L in the preceding 24 months.
- Subject has the ability and willingness to maintain their baseline diet, whether Phe-restricted or unrestricted for the duration of the trial, unless otherwise directed
Key Exclusion Criteria:
- Subjects with PKU that is not due to PAH deficiency
- Presence of anti-AAVHSC15 neutralizing antibodies
- ALT > ULN and AST > ULN
- Alkaline phosphatase > ULN.
- Total bilirubin > ULN, direct bilirubin > ULN
- Serum creatinine >1.5x ULN
- International normalized ratio (INR) > 1.2
- Hematology values outside of the normal range (hemoglobin <11.0 g/dL for males or <10.0 g/dL for females; white blood cells (WBC) <3,000/μL; absolute neutrophils <1500/μL; platelets <100,000/μL)
- Hemoglobin A1c >6.5% or fasting glucose >126 mg/dL
- Any clinically significant abnormal laboratory result at screening, in the opinion of the Investigator
- Contraindication to corticosteroid use or conditions that could worsen in the presence of corticosteroids, as assessed and determined by the investigator
- Previously received gene therapy for the treatment of any condition.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03952156
United States, California | |
Kaiser Permanente Los Angeles Medical Center | |
Los Angeles, California, United States, 90027 | |
Children's Hospital of Orange County | |
Orange, California, United States, 92868 | |
United States, Florida | |
University of South Florida | |
Tampa, Florida, United States, 33606 | |
United States, Georgia | |
Emory University Hospital | |
Atlanta, Georgia, United States, 30322 | |
United States, Illinois | |
Lurie Children's Hospital of Chicago | |
Chicago, Illinois, United States, 60611 | |
United States, Massachusetts | |
Boston Children's Hospital | |
Boston, Massachusetts, United States, 02115 | |
United States, New York | |
Icahn School of Medicine at Mount Sinai | |
New York, New York, United States, 10029 | |
United States, North Carolina | |
The University of North Carolina At Chapel Hill | |
Chapel Hill, North Carolina, United States, 27599 | |
United States, Ohio | |
Nationwide Children's Hospital | |
Columbus, Ohio, United States, 43205 | |
United States, Pennsylvania | |
Children's Hospital of Philadelphia | |
Philadelphia, Pennsylvania, United States, 19104 | |
UPMC Children's Hospital of Pittsburgh | |
Pittsburgh, Pennsylvania, United States, 15224 | |
United States, Texas | |
University of Texas Southwestern Medical Center | |
Dallas, Texas, United States, 75235 | |
United States, Utah | |
University of Utah | |
Salt Lake City, Utah, United States, 84108 |
Principal Investigator: | Olaf A Bodamer, M.D. | Boston Children's Hospital |
Responsible Party: | Homology Medicines, Inc |
ClinicalTrials.gov Identifier: | NCT03952156 |
Other Study ID Numbers: |
HMI-102-101 |
First Posted: | May 16, 2019 Key Record Dates |
Last Update Posted: | March 2, 2023 |
Last Verified: | February 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
PKU Phenylketonuria PAH Deficiency Hyperphenylalaninemia |
Phenylalanine Adeno Associated Virus AAVHSC15 |
Phenylketonurias Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases |
Nervous System Diseases Amino Acid Metabolism, Inborn Errors Metabolism, Inborn Errors Genetic Diseases, Inborn Metabolic Diseases |